Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays

查看全文 作　　者：Niccolo [1,3]Candelise;Matthias [1]Schmitz;Katrin [1]Thüne;Maria [1]Cramm;Alberto [4]Rabano;Saima [1,2]Zafar;Erik [5]Stoops;Hugo [5]Vanderstichele;Anna Villar-[1,6]Pique;Franc [1,6,7]Llorens;Inga [1]Zerr

机构地区：[1]Department of Neurology,University Medicine Goettingen and the German Center for Neurodegenerative Diseases(DZNE),Robert-Koch-Stra?e 40,37075 G?ttingen,Germany;[2]Biomedical Engineering and Sciences Department,School of Mechanical and Manufacturing Engineering(SMME),National University of Sciences and Technology(NUST),Islamabad,Pakistan;[3]Department of Experimental,Diagnostic and Speciality Medicine,University of Bologna,Bologna,Italy;[4]Departamento de Neuropatología y Banco de Tejidos(BT-CIEN),Fundación CIEN,Instituto de Salud Carlos III Centro Alzheimer Fundación Reina Sofíac,Valderrebollo n°5,28031 Madrid,Spain;[5]ADx NeuroSciences,Technologiepark 4,Ghent,Belgium;[6]CIBERNED(Network center for biomedical research of neurodegenerative diseases),Institute Carlos III,Madrid,Spain;[7]Bellvitge Biomedical Research Institute(IDIBELL),Hospitalet de Llobregat,Barcelona,Spain

出　　处：《Translational Neurodegeneration》索引2020年第9卷第1期,共16页

基　　金：The project was supported by the German Academic Exchange Service(DAAD)project 57421248;by the Alzheimer Forschung Initiative(AFI)project 17022;the Instituto Carlos Ⅲ(Miguel Servet programme—CP16/00041)to FL. 摘　　要：Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hallmarks ofαsynucleinopathies,such as Parkinson’s disease(PD)or dementia with Lewy bodies(DLB).Main body:Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism ofαsynucleinopathies and for the development of efficient therapeutic strategies.Based on the conversion and aggregation mechanism of α-synuclein,novel diagnostic tests,such as protein misfolding seeded conversion assays,e.g.the real-time quaking-induced conversion(RT-QuIC),had been developed.In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100%while the sensitivity varies between 70 and 100%among different laboratories.In addition,the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.Conclusion:The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols,cohorts and material etc..An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies. 关键词：RT-QuIC α-Synucleinopathies Protein misfolding Protein strains

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Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays

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